We report the discovery of 6,7-dimethoxy-4-(pyridin-3-yl)cinnolines as novel inhibitors of
phosphodiesterase 10A (PDE10A). Systematic examination and analyses of structure–activity-…

Our development of PDE10A inhibitors began with an HTS screening hit (1) that exhibited
both high p-glycoprotein (P-gp) efflux ratios in rat and human and poor metabolic stability. On …

We report the discovery of a novel series of biaryl ethers as potent and selective PDE10A
inhibitors. Structure–activity studies improved the potency and decreased Pgp-mediated efflux …

A radiolabeled tracer for imaging therapeutic targets in the brain is a valuable tool for lead
optimization in CNS drug discovery and for dose selection in clinical development. We report …

γ-Secretase modulators (GSMs) are potentially disease-modifying treatments for Alzheimer’s
disease. They selectively lower pathogenic Aβ42 levels by shifting the enzyme cleavage …

Introduction Phosphodiesterase 10A (PDE10A) is an intracellular enzyme responsible for the
breakdown of cyclic nucleotides which are important secondary messengers in the central …

Phosphodiesterase 10A (PDE10A) inhibitors have therapeutic potential for the treatment of
psychiatric and neurologic disorders, such as schizophrenia and Huntington’s disease. One …

We report our successful effort to increase the PDE3 selectivity of PDE10A inhibitor pyridyl
cinnoline 1 using a combination of computational modeling and structural–activity …

Deregulation of the receptor tyrosine kinase c-Kit is associated with an increasing number
of human diseases, including certain cancers and mast cell diseases. Interference of c-Kit …

Phosphodiesterase 10A (PDE10A) inhibitors have therapeutic potential for the treatment of
psychiatric and neurological disorders, such as schizophrenia and Huntington’s disease. …